chr8-143580675-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130053.5(EEF1D):​c.1541C>T​(p.Pro514Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Consequence

EEF1D
NM_001130053.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78
Variant links:
Genes affected
EEF1D (HGNC:3211): (eukaryotic translation elongation factor 1 delta) This gene encodes a subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This subunit, delta, functions as guanine nucleotide exchange factor. It is reported that following HIV-1 infection, this subunit interacts with HIV-1 Tat. This interaction results in repression of translation of host cell proteins and enhanced translation of viral proteins. Several alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. Related pseudogenes have been defined on chromosomes 1, 6, 7, 9, 11, 13, 17, 19.[provided by RefSeq, Aug 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2327736).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EEF1DNM_001130053.5 linkc.1541C>T p.Pro514Leu missense_variant Exon 8 of 10 ENST00000618139.4 NP_001123525.3 P29692-2D3DWK1B2RAR6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EEF1DENST00000618139.4 linkc.1541C>T p.Pro514Leu missense_variant Exon 8 of 10 5 NM_001130053.5 ENSP00000484536.2 P29692-2A0A087X1X7

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1541C>T (p.P514L) alteration is located in exon 8 (coding exon 6) of the EEF1D gene. This alteration results from a C to T substitution at nucleotide position 1541, causing the proline (P) at amino acid position 514 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.037
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.072
T;T;.;T;.;.;.;T;T;.;.;.;T;.;T;T;T;T;T;.
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.032
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.83
T;.;T;T;T;.;.;.;.;T;T;T;T;T;.;T;T;T;T;T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.23
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
2.0
M;M;.;.;.;.;.;M;M;.;.;.;.;.;.;.;.;.;.;.
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-2.7
D;D;D;D;D;D;D;D;D;D;D;.;D;D;N;N;N;D;D;D
REVEL
Benign
0.085
Sift
Uncertain
0.014
D;D;D;D;D;D;D;D;D;T;D;.;D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.055
T;T;T;D;T;T;D;T;T;T;D;T;.;T;T;T;.;.;T;.
Polyphen
0.24
B;B;P;B;.;P;.;B;B;.;.;.;.;.;.;.;.;.;.;.
Vest4
0.19
MutPred
0.19
.;.;.;Gain of helix (P = 0.0854);.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;
MVP
0.82
MPC
0.13
ClinPred
0.76
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-144662845; API